This proposal is aimed at studying the effects of various schedules of a given combination of drugs on the interaction among the drugs and between chemotherapy and immunotherapy in acute myelogenous leukemia of W/FU rats and BN leukemia of BN/Rij rats. These drug interactions which could be either synergistic, additive or antagonistic, will be monitored as increase in life span of tumor-bearing animals, pertuabation of cell cycle kinetics by pulse cytophotometry and survival (cloning ability) of leukemic and normal cells in culture (CFUC) and in the spleens of x-irradiated recipient rats (CFUS). We propose to isolate and use a tetraploid line of tumor cells in these studies so that the interaction between the leukemic and normal hematopoietic tissues can be studied with regard to kinetics and survival during the development of the disease as well as during the course of chemo- and immunotherapy. This feature would enable us not only to distinguish the leukemic cells on the basis of their DNA content but also separate them from the normal ones on the basis of cell size for CFU determinations. The combinations to be studied consist of two drugs with or without BCG which include ara-C with adriamycin, 6 thioguanine, methotrexate or cytoxan and methotrexate with adriamycin, 6-thioguanine or cytoxan. The results from these studies would show the role of proper drug schedules in combination chemotherapy of cancer and could serve as models in formulating drug schedules for the treatment of cancer patients. BIBLIOGRAPHIC REFERENCES: Rao, P.N., Wilson, B.A., and Puck, T.T. (1977). Premature Chromosome Condensation and Cell Cycle Analysis. J. Cell. Physiol.; in press. Sunkara, P.S., Rao, P.N., and Nishioka, K. (1977). Putrescine Biosynthesis in Mammalian Cells: Essential for DNA Synthesis but not for Mitosis. Biochem. Biophys. Res. Comm. in press.